The grand challenge addressed by the Penn Implementation Science Center in Cancer Control (ISC3) is to apply insights from behavioral economics to rapidly accelerate the pace at which we deploy evidence-based practices for patients with cancer, thereby improving cancer care quality and outcomes. Our Research Program, led by Drs. Beidas (implementation science expert) and Buttenheim (behavioral economics expert), will oversee the development and testing of implementation strategies within the Implementation Laboratory. Our implementation strategy design and testing approach includes the patient and clinician as targets, and is informed by behavioral economics to ?nudge? individuals to make optimal decisions for implementing evidence-based care. The Penn ISC3 is built on three principles. First, implementation science has not leveraged the rich literature from behav- ioral economics, which has elucidated many of the heuristics that underlie decisions and behaviors contributing to suboptimal health outcomes. Approaches from behavioral economics have not been applied systematically alongside implementation science to improve cancer care; these approaches aim to accelerate uptake of evi- dence-based practices. Second, implementation science has not applied methods to fail fast and learn quickly, which we will incorporate through the application of rapid cycle approaches. Third, research to identify mecha- nisms of the implementation strategies to improve uptake of evidence-based practices is in its infancy. The Research Program includes investigators with expertise in implementation science, behavioral economics, can- cer care delivery research, healthcare innovation, measurement, and mixed methods. In the first two years, we propose three Signature Pilot Projects (SPPs) and two Methods Projects that both support the SPPs and ad- vance the science of implementation with an eye towards rapid learning. SPP 1 (Jenssen/Leone) tests patient- and clinician-directed implementation strategies to increase referral to tobacco cessation programs in patients receiving cancer treatment. SPP 2 (Bekelman/Patel) tests patient- and clinician-directed implementation strate- gies to increase use of higher-value bone modifying agents in patients with advanced breast, lung, and prostate cancer. Common methods and measures link these projects to provide pooled data to accomplish our objectives of testing multilevel implementation strategies to elucidate mechanisms and targets. SPP 3 (Bekelman/Rendle), the most exploratory and high-reward SPP, will test a patient-directed implementation strategy that leverages artificial intelligence and machine learning to promote oral chemotherapy adherence and symptom management. Methods Project 1 will develop a toolkit for the application of rapid cycle approaches (Asch/Buttenheim); Methods Project 2 will use qualitative comparative analysis to characterize multilevel contextual variation and mechanisms (Barg/Rendle). The scientific advances to come out of the Research Program will have a significant public health impact, consistent with NCI priorities, by rapidly improving uptake of evidence-based practices to improve cancer care quality and outcomes for millions of Americans with cancer. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page